Anti-adalimumab antibodies in psoriasis: Lack of clinical utility and laboratory evidence

G. Lombardi, Silvia Perego, Veronica Sansoni, M. Diani, G. Banfi, G. Altomare

Research output: Contribution to journalArticle

Abstract

Objective: Adalimumab has proven effective in psoriasis; however, secondary failure may result from the drug's immunogenicity. Prevalence data on the immunogenicity of biologicals, and of adalimumab in particular, are highly variable. We investigated the prevalence of anti-adalimumab antibodies and the association with clinical indexes and tumour necrosis factor α (TNFα) serum levels in psoriatic patients. Design: Case-control, longitudinal. Setting: Single centre. Participants: Patient groups: I (n=20) receiving biological therapies after switching from adalimumab; II (n=30) ongoing adalimumab therapy; III (n=30) novel adalimumab therapy; IV (n=15) biological therapies other than adalimumab. Healthy subjects: (group V; n=15) never treated with immunosuppressants or biologicals. Interventions: All groups were tested at enrolment. Group II was also tested at 12 months, and group III at 1, 3, and 6 months. Primary and secondary outcome measures: Standard clinical evaluations (Psoriasis Area Severity Index (PASI)), blood samples and two-site ELISAbased measurement of serum adalimumab trough levels, anti-adalimumab antibodies and TNFα. Results: The false-positive rate was 23% for adalimumab detection and 22% for anti-adalimumab antibodies in patients naïve to adalimumab. Spurious positivity for anti-adalimumab antibodies (one-timepoint positivity in group III during follow-up) accounted for 33% of the total. The prevalence of antidrug antibodies was highest (87%) in group I patients. No correlations were found between the presence of anti-adalimumab antibodies or adalimumab levels and changes in PASI scores. Conclusions: High variability of results, high prevalence of false-positives and lack of association between anti-adalimumab antibodies and TNFα level/PASI score limit this assay's usefulness. Accurate clinical evaluation is key to early identification of treatment failures.

Original languageEnglish
Article numbere011941
JournalBMJ Open
Volume6
Issue number12
DOIs
Publication statusPublished - Dec 1 2016

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Psoriasis
Anti-Idiotypic Antibodies
Biological Therapy
Adalimumab
Tumor Necrosis Factor-alpha
Immunosuppressive Agents
Treatment Failure
Serum
Healthy Volunteers

ASJC Scopus subject areas

  • Medicine(all)

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Anti-adalimumab antibodies in psoriasis : Lack of clinical utility and laboratory evidence. / Lombardi, G.; Perego, Silvia; Sansoni, Veronica; Diani, M.; Banfi, G.; Altomare, G.

In: BMJ Open, Vol. 6, No. 12, e011941, 01.12.2016.

Research output: Contribution to journalArticle

Lombardi, G. ; Perego, Silvia ; Sansoni, Veronica ; Diani, M. ; Banfi, G. ; Altomare, G. / Anti-adalimumab antibodies in psoriasis : Lack of clinical utility and laboratory evidence. In: BMJ Open. 2016 ; Vol. 6, No. 12.
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abstract = "Objective: Adalimumab has proven effective in psoriasis; however, secondary failure may result from the drug's immunogenicity. Prevalence data on the immunogenicity of biologicals, and of adalimumab in particular, are highly variable. We investigated the prevalence of anti-adalimumab antibodies and the association with clinical indexes and tumour necrosis factor α (TNFα) serum levels in psoriatic patients. Design: Case-control, longitudinal. Setting: Single centre. Participants: Patient groups: I (n=20) receiving biological therapies after switching from adalimumab; II (n=30) ongoing adalimumab therapy; III (n=30) novel adalimumab therapy; IV (n=15) biological therapies other than adalimumab. Healthy subjects: (group V; n=15) never treated with immunosuppressants or biologicals. Interventions: All groups were tested at enrolment. Group II was also tested at 12 months, and group III at 1, 3, and 6 months. Primary and secondary outcome measures: Standard clinical evaluations (Psoriasis Area Severity Index (PASI)), blood samples and two-site ELISAbased measurement of serum adalimumab trough levels, anti-adalimumab antibodies and TNFα. Results: The false-positive rate was 23{\%} for adalimumab detection and 22{\%} for anti-adalimumab antibodies in patients na{\"i}ve to adalimumab. Spurious positivity for anti-adalimumab antibodies (one-timepoint positivity in group III during follow-up) accounted for 33{\%} of the total. The prevalence of antidrug antibodies was highest (87{\%}) in group I patients. No correlations were found between the presence of anti-adalimumab antibodies or adalimumab levels and changes in PASI scores. Conclusions: High variability of results, high prevalence of false-positives and lack of association between anti-adalimumab antibodies and TNFα level/PASI score limit this assay's usefulness. Accurate clinical evaluation is key to early identification of treatment failures.",
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