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 language | English |
|---|---|
| Article number | e011941 |
| Journal | BMJ Open |
| Volume | 6 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 1 2016 |
Fingerprint
ASJC Scopus subject areas
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Anti-adalimumab antibodies in psoriasis
T2 - Lack of clinical utility and laboratory evidence
AU - Lombardi, G.
AU - Perego, Silvia
AU - Sansoni, Veronica
AU - Diani, M.
AU - Banfi, G.
AU - Altomare, G.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85006055088&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85006055088&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2016-011941
DO - 10.1136/bmjopen-2016-011941
M3 - Article
AN - SCOPUS:85006055088
VL - 6
JO - BMJ Open
JF - BMJ Open
SN - 2044-6055
IS - 12
M1 - e011941
ER -