New strategies to address the pharmacodynamics and pharmacokinetics of tumor necrosis factor (TNF) inhibitors: A systematic analysis

Autoimmunity Reviews

Volumn 14, Issue 9, 2015, Pages 812-829

  Meroni, Pier Luigi ^a   Valentini, Gabriele ^b   Ayala, Fabio ^c   Cattaneo, Antonino ^d,f   Valesini, Guido ^e  

^a UNIVERSITY OF MILAN   (Italy)

^b SECOND UNIVERSITY OF NAPLES   (Italy)

^c UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^d SCUOLA NORMALE SUPERIORE   (Italy)

^e EUROPEAN BRAIN RESEARCH INSTITUTE   (Italy)

^f SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

Adalimumab; Anti drug detection; Drug bioavailability; Etanercept; Infliximab; Systematic review; TNF inhibitors

Indexed keywords

ADALIMUMAB; DRUG ANTIBODY; ETANERCEPT; INFLIXIMAB; IMMUNOGLOBULIN G; MONOCLONAL ANTIBODY; TNFR-FC FUSION PROTEIN; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RECEPTOR;

ANKYLOSING SPONDYLITIS; ANTIBODY PRODUCTION; ANTIBODY TITER; CLINICAL ASSESSMENT; CROHN DISEASE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG MECHANISM; HUMAN; IMMUNOASSAY; IMMUNOGENICITY; IMMUNOSUPPRESSIVE TREATMENT; INFORMATION RETRIEVAL; MEDLINE; PHARMACODYNAMICS; PHARMACOKINETICS; PSORIASIS; PSORIATIC ARTHRITIS; REVIEW; RHEUMATOID ARTHRITIS; SYSTEMATIC REVIEW; ANTAGONISTS AND INHIBITORS; TREATMENT OUTCOME;

ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; HUMANS; IMMUNOGLOBULIN G; RECEPTORS, TUMOR NECROSIS FACTOR; TREATMENT OUTCOME; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84938214020     PISSN: 15689972     EISSN: 18730183     Source Type: Journal    
DOI: 10.1016/j.autrev.2015.05.001     Document Type: Review

References (90)

1. Kodama S., Davis M., Faustman D.L. The therapeutic potential for tumor necrosis factor for autoimmune diseases: a mechanistically based hypothesis. Cell Mol Life Sci 2005, 62:1850-1862.
2. Knight D.M., Trinh H., Le J., Siegel S., Shealy D., McDonough M., et al. Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol Immunol 1993, 30:1443-1453.
3. Kempeni J. Preliminary results with early clinical trials with the fully human anti-TNFα monoclonal antibody D2E7. Rheum Dis 1999, 58:170-172.
4. Shealy D., Cai A., Lacy E., Nesspor T., Staquet K., Johns L., et al. Characterization of golimumab (CNTO 148), a novel monoclonal antibody specific for human TNFα. Ann Rheum Dis 2007, 66:151.
5. Peppel K., Crawford D., Beutler B. A tumor necrosis factor (TNF) receptor-IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity. J Exp Med 1991, 174:1483-1489.
6. Nesbitt A., Fossati G., Bergin M., Stephens P., Stephens S., Foulkes R., et al. Mechanism of action of certolizumab pegol (CDP870): in vitro comparison with other antitumour necrosis factor α agents. Inflamm Bowel Dis 2007, 13:1323-1332.
7. Infliximab [package insert]. Horsham, PA: Janssen Biotech, Inc.; November 2013.
8. Adalimumab [package insert]. North Chicago, IL: AbbVie Inc; May 2014.
9. Certolizumab [package insert]. Smyrna, GA: UCB, Inc.; October 2013.
10. Etanercept [package insert]. Thousand Oaks, CA: Amgen Inc.; 2013.
11. Golimumab [package insert]. Horsham, PA: Janssen Biotech, Inc.; August 2011.
12. Caporali R., Pallavicini F.B., Filippini M., Gorla R., Marchesoni A., Favalli E.G., et al. Treatment of rheumatoid arthritis with anti-TNF-alpha agents: a reappraisal. Autoimmun Rev 2009, 8:274-280.
13. Atzeni F., Benucci M., Sallì S., Bongiovanni S., Boccassini L., Sarzi-Puttini P. Different effects of biological drugs in rheumatoid arthritis. Autoimmun Rev 2013, 12:575-579.
14. Bendtzen K. Personalized medicine: theranostics (therapeutics diagnostics) essential for rational use of tumor necrosis factor-alpha antagonists. Discov Med 2013, 15:201-211.
15. Rosenblum H., Amital H. Anti-TNF therapy: safety aspects of taking the risk. Autoimmun Rev 2011, 10:563-568.
16. Atzeni F., Talotta R., Salaffi F., Cassinotti A., Varisco V., Battellino M., et al. Immunogenicity and autoimmunity during anti-TNF therapy. Autoimmun Rev 2013, 12:703-708.
17. Deehan M., Garcês S., Kramer D., Baker M.P., Rat D., Roettger Y., et al. Managing unwanted immunogenicity of biologicals. Autoimmun Rev July 2015, 14(7):569-574.
18. Vincent F.B., Morand E.F., Murphy K., MacKay F., Mariette X., Marcelli C. 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, 72:165-178.
19. Scheinfeld N. A comprehensive review and evaluation of the side effects of the tumor necrosis factor alpha blockers etanercept infliximab and adalimumab. J Dermatalog Treat 2004, 15:280-294.
20. Aikawa N.E., de Carvalho J.F., Silva C.A.A., Bonfá E. Immunogenicity of anti-TNF-α agents in autoimmune diseases. Clin. Rev. Allergy Immunol. 2010, 38:82-89.
21. Adisen E., Aral A., Aybay C., Gurer M.A. Anti-infliximab antibody status and its relation to clinical response in psoriatic patients: a pilot study. J Dermatol 2010, 37:708-713.
22. Afif W., Loftus E.V., Faubion W.A., Kane S.V., Bruining D.H., Hanson K.A., et al. Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease. Am J Gastroenterol 2010, 105:1133-1139.
23. Ainsworth M.A., Bendtzen K., Brynskov J. 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, 103:944-948.
24. Baert F., Noman M., Vermeire S., Van Assche G., D'Haens G., Carbonez A Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med 2003, 348:601-608.
25. Ben-Horin S., Waterman M., Kopylov U., Yavzori M., Picard O., Fudim E., et al. Addition of an immunomodulator to infliximab therapy eliminates antidrug antibodies in serum and restores clinical response of patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2013, 11:444-447.
26. Ben-Horin S., Yavzori M., Katz L., Kopylov U., Picard O., Fudim E., 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, 60:41-48.
27. de Vries M.K., Wolbink G.J., Stapel S.O., de Groot E.R., Dijkmans B.A., Aarden L.A., et al. Inefficacy of infliximab in ankylosing spondylitis is correlated with antibody formation. Ann Rheum Dis 2007, 66:133-134.
28. de Vries M.K., Wolbink G.J., Stapel S.O., de Vrieze H., van Denderen J.C., Dijkmans B.A., et al. Decreased clinical response to infliximab in ankylosing spondylitis is correlated with anti-infliximab formation. Ann Rheum Dis 2007, 66:1252-1254.
29. Ebert E.C., Das K.M., Mehta V., Rezac C. Non-response to infliximab may be due to innate neutralizing anti-tumour necrosis factor-alpha antibodies. Clin Exp Immunol 2008, 154:325-331.
30. Edrees A.F., Misra S.N., Abdou N.I. Anti-tumor necrosis factor (TNF) therapy in rheumatoid arthritis: correlation of TNF-alpha serum level with clinical response and benefit from changing dose or frequency of infliximab infusions. Clin Exp Rheumatol 2005, 23:469-474.
31. Finckh A., Dudler J., Wermelinger F., Ciurea A., Kyburz D., Gabay C., 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, 77:313-318.
32. Hanauer S.B., Wagner C.L., Bala M., Mayer L., Travers S., Diamond R.H., et al. Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn's disease. Clin Gastroenterol Hepatol 2004, 2:542-553.
33. Haraoui B., Cameron L., Ouellet M., White B. Anti-infliximab antibodies in patients with rheumatoid arthritis who require higher doses of infliximab to achieve or maintain a clinical response. J Rheumatol 2006, 33:31-36.
34. Hoffmann J.H., Hartmann M., Enk A.H., Hadaschik E.N. Autoantibodies in psoriasis as predictors for loss of response and anti-infliximab antibody induction. Br J Dermatol 2011, 165:1355-1358.
35. Kosmač M., Avčin T., Toplak N., Simonini G., Cimaz R., Curin Šerbec V. Exploring the binding sites of anti-infliximab antibodies in pediatric patients with rheumatic diseases treated with infliximab. Pediatr. Res. 2011, 69:243-248.
36. Mori S., Ueki Y. Primary lack of efficacy of infliximab therapy for rheumatoid arthritis: pharmacokinetic characterization and assessment of switching to tocilizumab. Mod Rheumatol 2011, 21:628-636.
37. Okuyama A., Nagasawa H., Suzuki K., Kameda H., Kondo H., Amano K., et al. Fcγ receptor IIIb polymorphism and use of glucocorticoids at baseline are associated with infusion reactions to infliximab in patients with rheumatoid arthritis. Ann Rheum Dis 2011, 70:299-304.
38. Jürgens M., Laubender R.P., Hartl F., Weidinger M., Seiderer J., Wagner J., et al. Disease activity, ANCA, and IL23R genotype status determine early response to infliximab in patients with ulcerative colitis. Am J Gastroenterol 2010, 105:1811-1819.
39. Pascual-Salcedo D., Plasencia C., Ramiro S., Nuño L., Bonilla G., Nagore D., et al. Influence of immunogenicity on the efficacy of long-term treatment with infliximab in rheumatoid arthritis. Rheumatology (Oxford) 2011, 50:1445-1452.
40. Plasencia C., Pascual-Salcedo D., Nuño L., Bonilla G., Villalba A., Peiteado D., et al. Influence of immunogenicity on the efficacy of longterm treatment of spondyloarthritis with infliximab. Ann Rheum Dis 2012, 71:1955-1960.
41. Seow C.H., Newman A., Irwin S.P., Steinhart A.H., Silverberg M.S., Greenberg G.R. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut 2010, 59:49-54.
42. Steenholdt C., Al-khalaf M., Brynskov J., Bendtzen K., Thomsen O.Ø., Ainsworth M.A. Clinical implications of variations in anti-infliximab antibody levels in patients with inflammatory bowel disease. Inflamm Bowel Dis 2012, 18:2209-2217.
43. Steenholdt C., Bendtzen K., Brynskov J., Thomsen O.Ø., Ainsworth M.A. Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn's disease. Scand J Gastroenterol 2011, 46:310-318.
44. van den Bemt B.J., den Broeder A.A., Snijders G.F., Hekster Y.A., van Riel P.L., Benraad B., et al. Sustained effect after lowering high-dose infliximab in patients with rheumatoid arthritis: a prospective dose titration study. Ann Rheum Dis 2008, 67:1697-1701.
45. van den Bemt B.J., den Broeder A.A., Wolbink G.J., Hekster Y.A., van Riel P.L., Benraad B., et al. Anti-infliximab antibodies are already detectable in most patients with rheumatoid arthritis halfway through an infusion cycle: an open-label pharmacokinetic cohort study. BMC Musculoskelet Disord 2011, 12:12.
46. van der Maas A., van den Bemt B.J., Wolbink G., van den Hoogen F.H., van Riel P.L., den Broeder A.A. 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.
47. Vultaggio A., Matucci A., Nencini F., Pratesi S., Parronchi P., Rossi O., et al. Anti-infliximab IgE and non-IgE antibodies and induction of infusion-related severe anaphylactic reactions. Allergy 2010, 65:657-661.
48. Wolbink G.J., Vis M., Lems W., Voskuyl A.E., de Groot E., Nurmohamed M.T., et al. Development of antiinfliximab antibodies and relationship to clinical response in patients with rheumatoid arthritis. Arthritis Rheum 2006, 54:711-715.
49. Bendtzen K., Geborek P., Svenson M., Larsson L., Kapetanovic M.C., Saxne T. Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab. Arthritis Rheum 2006, 54:3782-3789.
50. Imaeda H., Andoh A., Fujiyama Y. Development of a new immunoassay for the accurate determination of anti-infliximab antibodies in inflammatory bowel disease. J Gastroenterol 2012, 47:136-143.
51. Kopylov U., Mazor Y., Yavzori M., Fudim E., Katz L., Coscas D., et al. Clinical utility of antihuman lambda chain-based enzyme-linked immunosorbent assay (ELISA) versus double antigen ELISA for the detection of anti-infliximab antibodies. Inflamm Bowel Dis 2012, 18:1628-1633.
52. Steenholdt C., Svenson M., Bendtzen K., Thomsen O.Ø., Brynskov J., Ainsworth M.A. Severe infusion reactions to infliximab: aetiology, immunogenicity and risk factors in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2011, 34:51-58.
53. Svenson M., Geborek P., Saxne T., Bendtzen K. Monitoring patients treated with anti-TNF-alpha biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodies. Rheumatology 2007, 46:1828-1834.
54. van der Laken C.J., Voskuyl A.E., Roos J.C., Stigter van Walsum M., de Groot E.R., Wolbink G., et al. Imaging and serum analysis of immune complex formation of radiolabelled infliximab and anti-infliximab in responders and non-responders to therapy for rheumatoid arthritis. Ann Rheum Dis 2007, 66:253-256.
55. Bartelds G.M., de Groot E., Nurmohamed M.T., Hart M.H., van Eede P.H., Wijbrandts C.A., et al. Surprising negative association between Igg1 allotype disparity and anti-adalimumab formation: a cohort study. Arthritis Res Ther 2010, 12:R221.
56. Bartelds G.M., Krieckaert C.L., Nurmohamed M.T., van Schouwenburg P.A., Lems W.F., Twisk J.W., et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA 2011, 305:1460-1468.
57. Bartelds G.M., Wijbrandts C.A., Nurmohamed M.T., Stapel S., Lems W.F., Aarden L., et al. Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis. Ann Rheum Dis 2007, 66:921-926.
58. Bartelds G.M., Wijbrandts C.A., Nurmohamed M.T., Wolbink G.J., de Vries N., Tak P.P., et al. Anti-adalimumab antibodies in rheumatoid arthritis patients are associated with interleukin-10 gene polymorphisms. Arthritis Rheum 2009, 60:2541-2542.
59. Bender N.K., Heilig C.E., Dröll B., Wohlgemuth J., Armbruster F.P., Heilig B. Immunogenicity, efficacy and adverse events of adalimumab in RA patients. Rheumatol Int 2007, 27:269-274.
60. de Vries M.K., Brouwer E., van der Horst-Bruinsma I.E., Spoorenberg A., van Denderen J.C., Jamnitski A., et al. Decreased clinical response to adalimumab in ankylosing spondylitis is associated with antibody formation. Ann Rheum Dis 2009, 68:1787-1788.
61. Karmiris K., Paintaud G., Noman M., Magdelaine-Beuzelin C., Ferrante M., Degenne D., et al. Influence of trough serum levels and immunogenicity on long-term outcome of adalimumab therapy in Crohn's disease. Gastroenterology 2009, 137:1628-1640.
62. Krieckaert C.L., Nurmohamed M.T., Wolbink G.J. Methotrexate reduces immunogenicity in adalimumab treated rheumatoid arthritis patients in a dose dependent manner. Ann Rheum Dis 2012, 71:1914-1915.
63. Lecluse L.L., Driessen R.J., Spuls P.I., de Jong E.M., Stapel S.O., van Doorn M.B., et al. Extent and clinical consequences of antibody formation against adalimumab in patients with plaque psoriasis. Arch Dermatol 2010, 146:127-132.
64. Sandborn W.J., Hanauer S., Loftus E.V., Tremaine W.J., Kane S., Cohen R., et al. An open-label study of the human anti-TNF monoclonal antibody adalimumab in subjects with prior loss of response or intolerance to infliximab for Crohn's disease. Am J Gastroenterol 2004, 99:1984-1989.
65. van der Bijl A.E., Breedveld F.C., Antoni C.E., Kalden J.R., Kary S., Burmester G.R., et al. An open-label pilot study of the effectiveness of adalimumab in patients with rheumatoid arthritis and previous infliximab treatment: relationship to reasons for failure and anti-infliximab antibody status. Clin Rheumatol 2008, 27:1021-1028.
66. van Kuijk A.W., de Groot M., Stapel S.O., Dijkmans B.A., Wolbink G.J., Tak P.P. 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, 69:624-625.
67. van Schouwenburg P.A., Krieckaert C.L., Rispens T., Aarden L., Wolbink G.J., Wouters D. 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, 72:1680-1686.
68. West R.L., Zelinkova Z., Wolbink G.J., Kuipers E.J., Stokkers P.C., van der Woude C.J. Immunogenicity negatively influences the outcome of adalimumab treatment in Crohn's disease. Aliment Pharmacol Ther 2008, 28:1122-1126.
69. Hart M.H., de Vrieze H., Wouters D., Wolbink G.J., Killestein J., de Groot E.R., et al. Differential effect of drug interference in immunogenicity assays. J Immunol Methods 2011, 372:196-203.
70. van Schouwenburg P.A., Bartelds G.M., Hart M.H., Aarden L., Wolbink G.J., Wouters D. 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, 362:82-88.
71. van Schouwenburg P.A., Krieckaert C.L., Nurmohamed M., Hart M., Rispens T., Aarden L., et al. IgG4 production against adalimumab during long term treatment of RA patients. J Clin Immunol 2012, 32:1000-1006.
72. van Schouwenburg P.A., van de Stadt L.A., de Jong R.N., van Buren E.E., Kruithof S., de Groot E., et al. Adalimumab elicits a restricted anti-idiotypic antibody response in autoimmune patients resulting in functional neutralisation. Ann Rheum Dis 2013, 72:104-109.
73. Dore R.K., Mathews S., Schechtman J., Surbeck W., Mandel D., Patel A., et al. The immunogenicity, safety, and efficacy of etanercept liquid administered once weekly in patients with rheumatoid arthritis. Clin Exp Rheumatol 2007, 25:40-46.
74. Jamnitski A., Bartelds G.M., Nurmohamed M.T., van Schouwenburg P.A., van Schaardenburg D., Stapel S.O., et al. The presence or absence of antibodies to infliximab or adalimumab determines the outcome of switching to etanercept. Ann Rheum Dis 2011, 70:284-288.
75. Jamnitski A., Krieckaert C.L., Nurmohamed M.T., Hart M.H., Dijkmans B.A., Aarden L., et al. Patients non-responding to etanercept obtain lower etanercept concentrations compared with responding patients. Ann Rheum Dis 2012, 71:88-91.
76. Klareskog L., Gaubitz M., Rodríguez-Valverde V., Malaise M., Dougados M., Wajdula J. Assessment of long-term safety and efficacy of etanercept in a 5-year extension study in patients with rheumatoid arthritis. Clin Exp Rheumatol 2011, 29:238-247.
77. de Vries M.K., van der Horst-Bruinsma I.E., Nurmohamed M.T., Aarden L.A., Stapel S.O., Peters M.J., et al. Immunogenicity does not influence treatment with etanercept in patients with ankylosing spondylitis. Ann Rheum Dis 2009, 68:531-535.
78. Bendzen K. Anti-TNF-biotherapies: perspectives for evidence-based personalized medicine. Immunotherapy 2012, 4:1167-1169.
79. Bendzen K., Svenson M. Enzyme immunoassays and radioimmunoassay for quantification of anti-TNF biopharmaceuticals and anti-drug antibodies. Detection and Quantification of Antibodies to Biopharmaceutical 2011, John Willey & Sons, Hoboken, NJ, USA. 10.1002/9781118075685.ch5. M.G. Tovey (Ed.).
80. Lallemand C., Kavrochorianou N., Steenhaoldt C., Bendtzen K., Ainsworth M.A., Meritet J.-F., et al. Reporter gene assay for the quantification of the activity and neutralizing antibody response to TNFα antagonists. J Immunol Methods 2011, 373:229-239.
81. Steenholdt C., Brynskov J., Thomsen O.Ø., Munck L.K., Fallingborg J., Christensen L.A., et al. Secondary infliximab treatment failure in Crohn's disease: therapeutic implications of measuring drug and anti-drug antibodies by three different binding assays. 9th ECCO Congress 2013 2013, [Abstract P374].
82. Descotes J., Gouraud A. Clinical immunotoxicity of therapeutic proteins. Expert Opin Drug Metab Toxicol 2008, 4:1537-1549.
83. Dubey S., Kerrigan N., Mills K., Scott D.G. Bronchospasm associated with anti-TNF treatment. Clin Rheumatol 2009, 28:989-992.
84. Korswagen L.A., Bartelds G.M., Krieckaert C.L., Turkstra F., Nurmohamed M.T., van Schaardenburg D., et al. Venous and arterial thromboembolic events in adalimumab-treated patients with antiadalimumab antibodies: a case series and cohort study. Arthritis Rheum 2011, 63:877-883.
85. Garces S., Demengeot J., Benito-Garcia E. 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, 6:6.
86. Jani M., Barton A., Warren R.B., Griffiths C.E., Chinoy H. The role of DMARDs in the immunogenicity of TNF inhibitors in chronic inflammatory diseases. Rheumatology (Oxford) 2014, 53:213-222.
87. Klareskog L., van der Heijde D., de Jager J.P., Gough A., Kalden J., Malaise M., et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 2004, 363:675-681.
88. Mahil S.K., Arkir Z., Richards G., Lewis C.M., Barker J.N., Smith C.H. Predicting treatment response in psoriasis using serum levels of adalimumab and etanercept: a single-centre cohort study. Br J Dermatol 2013, 169:306-313.
89. Krieckaert C.L., Nair S.C., Nurmohamed M.T., van Dongen C.J., Lems W.F., Lafeber F.P., et al. Personalised treatment using serum drug levels of adalimumab in patients with rheumatoid arthritis: an evaluation of costs and effects. Ann Rheum Dis. 2015, 74:361-368.
90. Steenholdt C., Brynskov J., Thomsen O.O., Munck L.K., Fallingborg J., Christensen L.A., et al. Individualised therapy is more cost effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment: a randomised controlled trial. Gut 2014, 63:919-927.