Predicting treatment response in psoriasis using serum levels of adalimumab and etanercept: a single-centre, cohort study

被引:65
作者
Mahil, S. K. [1 ,2 ]
Arkir, Z. [3 ]
Richards, G. [3 ]
Lewis, C. M. [4 ]
Barker, J. N. [1 ,2 ]
Smith, C. H. [1 ,2 ]
机构
[1] Kings Coll London, Div Genet & Mol Med, St Johns Inst Dermatol, London SE1 9RT, England
[2] Guys & St Thomas NHS Fdn Trust, London SE1 9RT, England
[3] Guys & St Thomas NHS Fdn Trust, GSTS Pathol, London SE1 9RT, England
[4] Kings Coll London, Div Genet & Mol Med, London SE1 9RT, England
关键词
CLINICAL-RESPONSE; ANTI-INFLIXIMAB; DOUBLE-BLIND; RHEUMATOID-ARTHRITIS; PHASE-III; ANTIBODIES; IMMUNOGENICITY; THERAPY; EFFICACY; MODERATE;
D O I
10.1111/bjd.12341
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100227 [皮肤病学];
摘要
Background A substantial proportion of patients with psoriasis do not respond, or lose initial response to tumour necrosis factor- antagonists. One possible mechanism relates to subtherapeutic drug levels due to an immunogenic antibody response. Objectives To investigate the association between serum adalimumab and etanercept levels, antidrug antibody levels and clinical response in a cohort of patients with psoriasis using a commercially available enzyme-linked immunoassay. Methods In a single-centre cohort of 56 adults with chronic plaque psoriasis initiated on adalimumab or etanercept monotherapy between 2009 and 2011, drug and antidrug antibody levels were measured at the patients' routine clinic reviews (4, 12 and 24weeks of treatment and the last available observation). Patients' responses at 6months were stratified into responders [75% reduction in Psoriasis Area and Severity Index from baseline (PASI 75) or Physician's Global Assessment score of clear' or nearly clear'] and nonresponders (failure to achieve PASI 50). Results After 4weeks, adalimumab levels were significantly higher in responders compared with nonresponders (P=0003) and these higher levels were sustained at 12 and 24weeks. Anti adalimumab antibodies were detected in 25% of nonresponders (two of eight patients, average 225weeks' follow-up) and none of the responders (n=23, average 261weeks' follow-up). There was no significant association between etanercept levels and clinical response at 4weeks (P=0317) and no antietanercept antibodies were detected. Lack of serum trough levels may have resulted in underestimation of the prevalence of antidrug antibodies. Conclusions Early adalimumab drug level monitoring at 4weeks may be useful in predicting treatment response and potentially reduce drug exposure (and associated cost) with earlier review of treatment in those with low levels. No conclusions about the value of etanercept drug monitoring can be made due to the paucity of data. Larger studies are now required to assess the clinical utility and cost-effectiveness of these assays in personalizing therapy in psoriasis.
引用
收藏
页码:306 / 313
页数:8
相关论文
共 34 条
[1]
Immunogenicity of anti-tumor necrosis factor antibodies - toward improved methods of anti-antibody measurement [J].
Aarden, Lucien ;
Ruuls, Sigrid R. ;
Wolbink, Gertjan .
CURRENT OPINION IN IMMUNOLOGY, 2008, 20 (04) :431-435
[2]
Anti-infliximab antibody status and its relation to clinical response in psoriatic patients: A pilot study [J].
Adisen, Esra ;
Aral, Arzu ;
Aybay, Cemalettin ;
Gurer, Mehmet Ali .
JOURNAL OF DERMATOLOGY, 2010, 37 (08) :708-713
[3]
Immunogenicity of Anti-TNF-α Agents in Autoimmune Diseases [J].
Aikawa, Nadia Emi ;
de Carvalho, Jozelio Freire ;
Almeida Silva, Clovis Artur ;
Bonfa, Eloisa .
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY, 2010, 38 (2-3) :82-89
[4]
Ballet V, 2012, J CROHNS COLITIS, V6, pS6, DOI DOI 10.1016/S1873-9946(12)60012-9
[5]
Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis [J].
Bartelds, Geertje M. ;
Wijbrandts, Carla A. ;
Nurmohamed, Michael T. ;
Stapel, Steven ;
Lems, Willem F. ;
Aarden, Lucien ;
Dijkmans, Ben A. C. ;
Tak, Paul Peter ;
Wolbink, Gerrit Jan .
ANNALS OF THE RHEUMATIC DISEASES, 2007, 66 (07) :921-926
[6]
Development of Antidrug Antibodies Against Adalimumab and Association With Disease Activity and Treatment Failure During Long-term Follow-up [J].
Bartelds, Geertje M. ;
Krieckaert, Charlotte L. M. ;
Nurmohamed, Michael T. ;
van Schouwenburg, Pauline A. ;
Lems, Willem F. ;
Twisk, Jos W. R. ;
Dijkmans, A. C. ;
Aarden, Lucien ;
Wolbink, Gerrit Jan .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2011, 305 (14) :1460-1468
[7]
Early serial trough and antidrug antibody level measurements predict clinical outcome of infliximab and adalimumab treatment [J].
Casteele, N. Vande ;
Ballet, V. ;
Van Assche, G. ;
Rutgeerts, P. ;
Vermeire, S. ;
Gils, A. .
GUT, 2012, 61 (02) :321-321
[8]
Etanercept Concentration in Patients with Rheumatoid Arthritis and Its Potential Influence on Treatment Decisions: A Pilot Study [J].
Daien, Claire Immediato ;
Daien, Vincent ;
Parussini, Ermis ;
Dupuy, Anne-Marie ;
Combe, Bernard ;
Morel, Jacques .
JOURNAL OF RHEUMATOLOGY, 2012, 39 (08) :1533-1538
[9]
Immunogenicity does not influence treatment with etanercept in patients with ankylosing spondylitis [J].
de Vries, M. K. ;
van der Horst-Bruinsma, I. E. ;
Nurmohamed, M. T. ;
Aarden, L. A. ;
Stapel, S. O. ;
Peters, M. J. L. ;
van denderen, J. C. ;
Dijkmans, B. A. C. ;
Wolbink, G. J. .
ANNALS OF THE RHEUMATIC DISEASES, 2009, 68 (04) :531-535
[10]
Dore RK, 2007, CLIN EXP RHEUMATOL, V25, P40